Taking account of fish welfare: lessons from aquaculture

This paper explores the possibility that lessons learned from aquaculture might contribute to current debate on welfare and fisheries. After looking briefly at the history of research interest in the welfare of farmed fishes, some implications of using different definitions of and approaches to the concept of welfare are discussed. Consideration is given to the way in which the aquaculture industry has responded to public concern about fish welfare and, for cases where these responses have been effective, why this might be the case. Finally, possible cross‐over points between aquaculture and fisheries in the context of fish welfare, as well as experience and expertise that might be shared between these two areas, are identified.     

Highly variable flowering time in Orchis ustulata (Orchidaceae): consequences for population dynamics

Two subspecies of Orchis ustulata differ considerably in their flowering time, but in only a few morphometric parameters; this makes the rank of these taxa problematic. The flowering time was not affected by replanting individuals to another habitat, including to the habitat of the other subspecies. In this study, populations from both subspecies were studied, measuring 464 marked genets during 5–6 years. Populations with different flowering times exhibited notable differences in their local distribution areas and the mean height of specimens. In the late-flowering populations the proportion of dormant plants is higher and the proportion of vegetatively propagated shoots lower than in the early-flowering ones. Going to (or staying) dormant is the biggest possibility in all stage groups. Flowering is more likely to be followed by dormancy than vegetative stage, but setting fruit does not affect the possibility. Vegetative propagation may play an important role in keeping the populations viable. Vegetative growth is more pronounced on stony soils.     

Monovalent IgG4 molecules

Antibodies have become the fastest growing class of biological therapeutics, in part due to their exquisite specificity and ability to modulate protein-protein interactions with a high biological potency. The relatively large size and bivalency of antibodies, however, limits their use as therapeutics in certain circumstances. Antibody fragments, such as single-chain variable fragments and antigen binding-fragments, have emerged as viable alternatives, but without further modifications these monovalent formats have reduced terminal serum half-lives because of their small size and lack of an Fc domain, which is required for FcRn-mediated recycling. Using rational engineering of the IgG4 Fc domain to disrupt key interactions at the CH3-CH3 interface, we identified a number of point mutations that abolish Fc dimerization and created half-antibodies, a novel monovalent antibody format that retains a monomeric Fc domain. Introduction of these mutations into an IgG1 framework also led to the creation of half-antibodies. These half-antibodies were shown to be soluble, thermodynamically stable and monomeric, characteristics that are favorable for use as therapeutic proteins. Despite significantly reduced FcRn binding in vitro, which suggests that avidity gains in a dimeric Fc are critical to optimal FcRn binding, this format demonstrated an increased terminal serum half-life compared with that expected for most alternative antibody fragments.     

Erythropoietin induction of tissue inhibitors of metalloproteinase-1 expression and secretion is mediated by mitogen-activated protein kinase and phosphatidylinositol 3-kinase pathways.

In the present study, we demonstrate that erythropoietin (Epo) induces the expression and the release of tissue inhibitors of metalloproteinase-1 (TIMP-1) in a time- and dose-dependent manner in Epo-dependent cell line UT-7 cells and in normal human erythroid progenitor cells from cord blood (CD36+) and required de novo protein synthesis. TIMP-1 was not expressed in the absence of Epo. Inhibition of the mitogen-activated protein kinase pathway by the specific inhibitors PD98059 and U0126 and of phosphatidylinositol 3-kinase by LY294002, strongly inhibited Epo-induced TIMP-1 expression and secretion. In the absence of Epo, both latent and active forms of matrix metalloproteinase-9 (MMP-9) were secreted into media. Upon Epo stimulation, MMP-9 and pro-MMP-9 secretion was inhibited in a dose-dependent manner parallel to TIMP-1 induction. The addition of PD98059, U0126, and LY294002 in the presence of Epo restored MMP-9 production in UT-7 and CD36+ cells. Our findings strongly suggest an inversely coordinated regulation of the TIMP-1 gene and MMP-9 production by Epo via mitogen-activated protein kinase and phosphatidylinositol 3-kinase pathways.